SiRNA Induced Transcriptional Silencing Of HIV-1: Elucidating The Mechanisms And Exploring Options For Delivery
Funder
National Health and Medical Research Council
Funding Amount
$512,631.00
Summary
Current drug therapy for HIV is for life We have discovered a set of molecules that will turn off the ability of HIV to reproduce itself. These molecules are from a new family of RNA molecules . A single dose of these molecules suppress the ability of the virus to reproduce itself for more than a month. Further we have found ways of extending this supressive ability to greater than one year. These studies will tell us how these molecules work and how they might be effectively administered.
SiRNA Induced TGS Of Retroviruses: Elucidation Of Underlying Mechanisms And Their Application In Animal Models
Funder
National Health and Medical Research Council
Funding Amount
$371,502.00
Summary
AIMS To elucidate changes in DNA that accompany suppression of HIV growth caused by certain unusual RNA molecules that turn off the ability of HIV to reproduce and make the virus dormant within the infected cell. While we have discovered RNA molecules that can do this to HIV in the test tube, we wish to develop similar molecules that can be used in animal models, so that we can decide whether this technology can be developed for use in humans. We also wish to understand more clearlky the mechani ....AIMS To elucidate changes in DNA that accompany suppression of HIV growth caused by certain unusual RNA molecules that turn off the ability of HIV to reproduce and make the virus dormant within the infected cell. While we have discovered RNA molecules that can do this to HIV in the test tube, we wish to develop similar molecules that can be used in animal models, so that we can decide whether this technology can be developed for use in humans. We also wish to understand more clearlky the mechanisms underlying this effect. BACKGROUND These RNA molecules can suppress a range of pathogenic human viruses including HIV-1 in the test tube. Our novel approach appears to induce changes that are long lasting and are less susceptible to mutations by the virus that allow it to become resistant to other therapeutic strategies. RESEARCH PLAN Initially more work will be done in tissue culture to determine the optimal design of these molecules and the best way to administer them. The most promising of these designs will be tested in small groups of infected animals as a preliminary demonstration of efficacy. In parallel experiments will be performed to elucidate the mechanisms undelying the suppressive effects of these molecules. OUTCOMES AND SIGNIFICANCE This work will lead to a significant increase in our understanding of the way replication of HIV is regulated and will develop a promising new therapeutic strategy for this virus that may be applicable to other conditions.Read moreRead less
The Role Of Aire In Immunological Tolerance And Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$434,134.00
Summary
The immune system is designed to protect us from foreign pathogens such as bacteria, viruses and parasites. This is achieved through lymphocytes which recognise foreign pathogens. However in 5-6% of the population the immune system attacks the host and induces autoimmunity. We aim to understand the mechanisms which control the production of self-reacting lymphocytes and how we may reduce the incidence of autoimmunity.
RNA Interference And Retigabine Therapy Protect Against Hereditary Hearing Loss
Funder
National Health and Medical Research Council
Funding Amount
$370,522.00
Summary
The preservation of hearing function is central to the treatment of individuals who are genetically predisposed to hearing loss. At present only synthetic hearing aids and cochlear implants can provide functional improvement, albeit sub-optimal. The studies described here will seek to prevent hearing loss by reducing the damaging effects of defective genes. Gene therapies that reduce the effect of these defective genes and a drug that enhances the activity of functional genes will be developed.
An Integrated Approach For The Efffective Adoptive Immunotherapy Of Cancer
Funder
National Health and Medical Research Council
Funding Amount
$468,119.00
Summary
Killer T lymphocytes can penetrate tumors and their transfer into cancer patients has demonstrated some encouraging results, but this form of immunotherapy remain ineffective in most cancer patients. We propose to improve the tumor trafficking and anti-tumor activities of killer cells by genetically engineering them with proteins that will enable them to recognise and destroy cancer cells. The outcomes of this project will validate this novel approach for treatment of cancer patients.
Treatment Of Genetic Liver Disease By Homologous Recombination In Vivo, Coupled With A Pharmoco-genetic Strategy For Selective Expansion Of Genetically Repaired Hepatocytes
Funder
National Health and Medical Research Council
Funding Amount
$920,836.00
Summary
This project seeks to exploit recent advancements in our ability to precisely “edit” and correct mutations underlying human genetic diseases. To improve therapeutic efficiencies of the system, we will deliver the technology using highly efficient virus-based systems and apply a novel post-repair selection process to preferentially repopulate the liver with gene-repaired cells. Demonstration of the strategy in a humanised mouse model will provide important preclinical data for human applications.
GENETIC MANIPULATION OF TUMOURS TO INDUCE IMMUNE REJECTION
Funder
National Health and Medical Research Council
Funding Amount
$396,342.00
Summary
The ability to be able to modify tumour growth and bring about tumour rejection by activating the host immune system is a prime objective in many laboratories throughout the world. Our aim is to take advantage of the considerable advances in molecular technology of recent years to develop effective approaches to the modification of tumour cells so that their growth can be inhibited in vivo. The project has three main aims: (i) to identify combinations of genes which, when administered to or expr ....The ability to be able to modify tumour growth and bring about tumour rejection by activating the host immune system is a prime objective in many laboratories throughout the world. Our aim is to take advantage of the considerable advances in molecular technology of recent years to develop effective approaches to the modification of tumour cells so that their growth can be inhibited in vivo. The project has three main aims: (i) to identify combinations of genes which, when administered to or expressed in tumour cells will induce protective immune responses against the tumour (ii) to investigate the effectiveness of combination approaches to gene therapy whereby genetic manipulations which cause destruction of tumour cells, or inhibition of blood vessel growth in tumours can be combined with administration of immunologically relevant genes to enhance tumour destruction (iii) to identify molecules which can act as target tumour antigens for the immune response or which are involved in promoting tumour survival so that these genes may be manipulated to enhance the development of anti-tumour immunity. The model we will use to investigate these issues will be malignant mesothelioma (MM). This tumour type is currently untreatable and is resistant to all available forms of therapy. Achievement of the aims described above would lead to the capacity for early treatment of MM. The identification of suitable target antigens has the potential to lead to vaccination protocols for therapy or as a preventative measure. Furthermore, the principles defined in this project will be applicable to the treatment of a variety of other solid tumours which are currently resistant to conventional therapy.Read moreRead less